Recombinogenic Effect of the Ternary Complex of Copper(II) with Doxycycline and 1,10-Phenanthroline on Somatic Cells of Drosophila melanogaster

In the search for new anti-tumor agents, exploiting features such as the flexibility of coordination modes of metals have become an alternative strategy for synthesizing pharmaceuticals. It has been shown that the CuDP (copper(II), doxycycline, and 1,10-phenanthroline) complex cleaves DNA strands by an oxidative mechanism and by intercalating the major groove, resulting in a cytotoxic action. The objective of this study was to assess the mutagenic/recombinogenic effects of the CuDP complex in vivo using the SMART (Somatic Mutation and Recombination Test) in Drosophila melanogaster. Treatments were carried out with third instar larvae at the standard cross and high bioactivation cross using three concentrations of CuDP (6.92, 13.84 or 27.67 mM). The mutagenic doxorubicin (0.4 mM) was used as a positive control and reverse osmosis water as a negative control. For each compound, marked trans-heterozygous and balanced heterozygous individuals were analyzed to determine the mutational and recombinogenic events occurring in the cells. We found that CuDP significantly increased the frequencies of mutant cells in both standard and high bioactivation crosses, mostly by induction of recombination. These data show that CuDP is a direct recombinogenic agent that is independent of bioactivation.